Process and apparatus for the combinatorial preparation of mixtures, and use of these

ABSTRACT

The present invention relates to a continuous process for the preparation of mixtures from a wide variety of components, and also to an apparatus for carrying out the process. The process encompasses the steps of:  
     a) charging the individual components to storage vessels,  
     b) introducing each individual component by way of a conveying device for this component into a mixing device,  
     c) varying the conveying rate of at least one conveying device in such a way that this conveying rate varies periodically between a lower and an upper limiting value, and  
     d) mixing the individual components in the mixing device.  
     An example of an application of the invention is the preparation of substance libraries for high-throughput screening in the plastics industry, in particular of mixtures of polymers with one another, and of mixtures of polymers with additives.

[0001] The present invention relates to a process for the combinatorialpreparation of mixtures of chemical compounds, for example for thepreparation of plastics mixtures suitable for high-throughput screening,and to an apparatus suitable for carrying out this process.

[0002] A number of automatic apparatuses have been developed forpreparing mixtures of chemical compounds. For example, U.S. Pat. No.4,595,496 describes an apparatus for the controlled feed to an apparatusfor liquid chromatography, in which the liquids to be applied arecharged to individual storage devices and are fed by way of supply linesand a pump to the chromatography column. The feed takes place by meansof a pump. In each supply line there is a valve which is activatedselectively and periodically. This permits attenuation of the variationsbrought about by the operation of the pump in the conveying rate of themixture fed.

[0003] The use of highly automated combinatorial methods to test theactivity of substances is a well-established constituent of research inthe sectors of pharmaceuticals and plant protection. The expression“combinatorial methods” generally refers to the production of a largenumber of chemically different compounds or mixtures and the subsequentrapid testing of these substance libraries for one or more properties.The synonymous term high-throughput screening is also used for thesemethods, because, alongside other advantages, they especially permit amarked increase in the speed of sample throughput. For example, use ofthese methods permits the activity of some tens of thousands ofsubstances to be checked every day in searches for active ingredients.Examples of the use of combinatorial methods are given by Lowe, J C SReviews, 309-317 (1995), 20 N. K. Terreft, Combinatorial Chemistry,Oxford University Press, Oxford, 1998, Combinatorial Chemistry andMolecular Diversity in Drug Discovery (eds.: E. M. Gordon, J. F.Kerwin), Wiley, New York, 1998.

[0004] Recently, these methods of combinatorial chemistry andhigh-throughput screening have received increasing attention inmaterials science, for example in the development of materials withoptical uses, or the discovery of new catalysts. An example of anoverview of these relatively new developments is found in the article byB. Jandeleit, D. J. Schäfer, T. S. Powers, H. W. Turner, W. H. Weinbergin Angewandte Chemie 1999, 111, 2648-2689.

[0005] Combinatorial methods have hitherto been very little used inresearch and development in the formulations sector, particularly inpolymer formulations.

[0006] The approaches described hitherto for the production and testingof substance libraries, including those for polymers or polymerformulations, are based on discrete, spatially separate containers(compartments) in which the mixtures are produced and then tested.

[0007] U.S. Pat. No. 5,985,356 describes the production and screening ofvarious inorganic or organic materials. It also describes thecopolymerization of styrene with acrylonitrile in toluene in anarrangement composed of compartments of size 3×3×5 mm. This requirescomplicated apparatuses for precise metering of monomers and initiator.

[0008] WO-A-99/52,962 describes a method for preparing alternatingcopolymers. In this, by way of example, the diol component and,respectively, the dicarboxylic acid components are varied systematicallyin an arrangement of 8 times 14 reaction vessels, and the resultantcopolymers are studied for selected properties.

[0009] WO-A-00/40331 describes an apparatus and a combinatorial methodfor the discovery of catalysts and polymers. It uses an apparatus forpolymerizing monomers in reactors arranged in parallel.

[0010] A discussion paper from the National Institute of Standards andTechnology (M. R. Nyden, J. W. Gilman, Proceedings, Fire RetardantChemicals Association, Mar. 12-15, 2000, Washington, D.C., 1-5 pp. 2000)mentions the continuous production of polymer formulations. (Internetaddress: http:/fire.nist.gov/bfrlpubs/fire00/PDF/f00017.pdf).

[0011] That publication discusses a process for continuous productionand testing of polymer formulations with flame retardants, proposing forthat purpose a system composed of a computer-controlled gravimetricsolids feed and an extruder which is not specified in any furtherdetail. The arrangement is intended to extrude polymers withflame-retardant additives in concentrations programmed in advance, thesethen being analyzed on-line and tested for fire performance.

[0012] The variation in concentration of the flame-retardant additive isintended to take place deterministically by way of thecomputer-controlled gravimetric feed unit in the previously-setconcentration steps, without covering the entire phase space.

[0013] A phase space includes all of the theoretically possiblecompositions of a multicomponent system. It can be represented as amultidimensional space with orthogonal coordinates which give theconcentrations of the components making up the mixture. In the case of amixture of, for example, five components, a point in thefive-dimensional phase space is unambiguously defined by way of the datafor the concentrations of the five components.

[0014] There is a limit to the precision with which phase spaces can bedepicted. Because any multicomponent system has an infinite number ofcompositions, practical operations have to be carried out with limitedcompositional resolution. The higher the desired compositionalresolution, the greater the number of different-concentration mixturesthat have to be produced.

[0015] None of the processes known hitherto covers the entire phasespace or selected portions of the phase space at a prescribed level ofresolution during the preparation of mixtures.

[0016] It is an object of the present invention to provide a process ofthis type and an apparatus suitable for carrying out the process.

[0017] A further object of the present invention consists in providing aprocess for the high-throughput screening of multicomponent formulations(at least two components).

[0018] A further object of the present invention consists in theprovision of a process which can, in a simple manner, set thecompositional resolution of mixtures as desired, in order to minimizethe cost for the apparatus and time needed for a given task.

[0019] The invention provides a process for the continuous preparationof mixtures from at least two components, encompassing the steps of:

[0020] a) charging the individual components to storage vessels,

[0021] b) introducing each individual component by way of a conveyingdevice for that component into a mixing device,

[0022] c) varying the conveying rate of at least one conveying device insuch a way that this conveying rate varies periodically between a lowerand an upper limiting value, and

[0023] d) mixing the individual components in the mixing device.

[0024] The achievement of the abovementioned objects is described by wayof example for a system with n components, using the diagram shown inFIG. 1.

[0025] Components 1 to n are present in the storage vessels C₁ to C_(n),component i being in vessel C_(i). Each vessel C_(i) has been connectedby way of a conveying apparatus (e.g. a pump) P_(i) to a mixing device(hereinafter also termed mixer M). The finished multicomponent mixturemay be further used at the outlet from the mixer.

[0026] To cover the entire phase space, the conveying rate CR(t)(CR(t)=dV/dt) [V=volume conveyed per unit of time; t=time] of theindividual conveying devices (e.g. pumps) is controlled as a function oftime. All of the conveying devices here are individually controllableand may follow different conveying rate/time functions CR(t). The natureof the periodic conveying rate/time function CR(t) may be that of anydesired periodic function, or else may be a constant, but at least oneof these conveying rate/time functions CR(t) has to be periodic, and atleast one of these conveying rate/time functions is non-pulsed(CR(t)<∞).

[0027] The process of the invention permits the entire phase space of amixture of prescribed components to be covered with any desiredprescribed precision.

[0028] At least the conveying rate of one conveying device is variedperiodically. The conveying rates of two or more conveying devices arepreferably varied periodically, the frequencies of the variationsdiffering from one another.

[0029] Particular preference is given to a process in which thevariation of the conveying rate of one conveying device continuouslyrises or falls, and wherein the variation in the conveying rate of allof the other conveying devices is periodic.

[0030] Particular preference is also given to a process in which thevariation of the conveying rate of at least one conveying device,preferably of all of the periodic variations, corresponds to a sawtoothfunction or a sine function, the periods thereof preferably beingconstant over time.

[0031] Very particular preference is given to a process in which thevariation of the conveying rate of at least one conveying devicecorresponds to a periodic step function whose periods and step intervalsare preferably constant over time.

[0032] In another, particularly preferred, version of the process of theinvention, the periods or step intervals for the variation of theconveying rates of the individual conveying devices are an integralmultiple of a base period, where the ratio of any two desired periods orstep intervals for the variation of the conveying rate of the conveyingdevices, or the ratio of a period and a step interval for the variationof the conveying rate of two conveying devices, is preferably equal tohalf of a whole number, and is in particular 0.5, or 1.5, or 2.5.

[0033] The periods or step intervals for the variations of the conveyingrates of the individual conveying devices are preferably an integralmultiple of a base period, and the minimum period or step interval maybe selected as desired.

[0034] The periods or step intervals for the variation of the conveyingrates of the individual conveying devices are preferably held constantover time.

[0035] The phase shifts of the periods or of the step intervals for thevariation of the conveying rates of the individual conveying devices arepreferably held constant over time.

[0036] The phase shifts of the periods or step intervals of theconveying rates of the individual conveying devices are veryparticularly preferably held equal to zero.

[0037] The following process measures have proven particularlysuccessful and may be used individually or in a combination in one ormore of these measures:

[0038] A) one conveying device is operated in continuously rising orfalling mode;

[0039] B) all of the other conveying devices follow periodic functions;

[0040] C) the frequencies of the conveying apparatuses for theindividual components differ from one another;

[0041] D) the ideal function for a conveying device is a sawtoothfunction or a sine function;

[0042] E) the ideal functions for all of the other conveying devices areperiodic step functions;

[0043] F) the periods and step intervals are preferably constant overtime;

[0044] G) the ratio of any two desired periods or step intervals, or theratio of a period and a step interval, is preferably half of a wholenumber (e.g. 0.5, or 1.5, or 2.5);

[0045] H) the frequency ratio is proportional to the desiredcompositional resolution;

[0046] I) all of the periodic functions preferably start with theminimum conveying rate CR(t=0)=CR_(min);

[0047] J) the phase shift of any two desired periodic functions withrespect to one another may likewise be freely selected (but ispreferably equal to zero in the case of the step functions);

[0048] K) the maximum conveying rate of the conveying apparatuses(amplitude of the periodic function), in relation one to the other,depends on the desired compositions;

[0049] L) the resolution of the compositions is proportional to thenumber of concentrations set between the minimum for the metering methodand the maximum value.

[0050] The minimum frequency for the periodic conveying rate/timefunctions CR(t) may be selected as desired, whereas the maximumfrequency depends on parameters of the apparatus, of the mixingcomponents, or of the mixture, for example on the substance to bemetered, on the conveying device, and on the axial dispersion in themixer.

[0051] In another preferred method of operation, the total conveyingrate of all of the conveying devices is constant over time.

[0052]FIGS. 2a and 2 b illustrate these preferred procedures set out initems A) to L). The conveying rate/time functions CR1(t) [FIG. 2a)] andCR2(t) [FIG. 2b)] are shown for two components, the time (in unspecifiedunits) being plotted on the abscissa and the concentrations C₁ and C₂,respectively, of components 1 and 2 (in unspecified units) being plottedon the ordinate.

[0053] This gives the phase space diagram shown in FIG. 3, whereabscissa and ordinate, respectively, show the concentration C₁ and C₂ ofcomponents 1 and 2, respectively, in the resultant composition.

[0054] The process of the invention permits any desired mixtures to beprepared from any desired conveyable substances, preference being givento mixtures of liquids, conveyable solids, and/or gases.

[0055] It is preferable to prepare mixtures from fluid solids, and/orpolymer melts, and/or masterbatches.

[0056] Examples of components of the mixtures to be prepared are any ofthe inorganic or organic materials which may be bonded by any desiredbonds, for example by ionic bonds, covalent bonds, or by complexing.

[0057] Examples of inorganic materials are metals, semimetals, or metalalloys, or metal salts, or else the oxides, sulfides, sulfites,sulfates, phosphates, or halides of metals or of semimetals.

[0058] Components of the mixtures to be prepared may also be ceramics.

[0059] Examples of organic materials are compounds whose mainconstituents are carbon and hydrogen and in which, where appropriate,relatively small proportions of oxygen, nitrogen, phosphorus, and/orother elements are also present.

[0060] These may be biological materials, or in particularnon-biological materials. Besides low-molar-mass compounds, for examplewith molar mass up to 500 g/mol, use is made of high-molecular-weightcompounds, in particular polymers. Besides the traditional organicmaterials, use may also be made of organometallic materials.

[0061] The components of the mixtures to be prepared may have anydesired properties, examples being electrical conductors (includingsuperconductors), semiconductors, or insulators, and/or thermalconductors or insulators, or may have diamagnetic, paramagnetic, orferromagnetic properties.

[0062] The process of the invention can also meter two or more additivessimultaneously in varying concentration into a screening experiment. Forexample, simultaneous variation of the concentration of the additivescan generate a substance library.

[0063] The mixtures prepared by the process of the invention mayencompass a partial volume (where appropriate with a relatively highnumber of dimensions) of the phase diagram of a multicomponent mixture.These are therefore suitable for wide-ranging high-throughput screening.It is possible here to encompass concentration ranges smaller than 1%for individual constituents of a mixture.

[0064] To carry out high-throughput screening, the mixtures preparedcombinatorially in the mixing assembly may be continuously converted toa form amenable to further processing and testing.

[0065] One advantageous variation of the invention is a process for thecontinuous preparation of mixtures from at least one thermoplasticpolymer and at least one additive, wherein at least one thermoplasticpolymer is fed continuously or in a succession of pulses to a mixingassembly, melted, and mixed with one or more additives, one or moreadditives being thus fed to the mixing assembly in one or moresuccessions of pulses, the polymer mixture is continuously dischargedfrom the mixing assembly, and is transformed into a form amenable tofurther processing and testing.

[0066] Another advantage of the mixtures prepared by the presentinvention is that the continuously prepared product can readily bedivided into discrete fractions of any desired size, whereas theprocesses of the prior art can, by virtue of the process itself, onlygive discrete fractions whose properties have to be planned individuallyprior to carrying out the experiment, and which are not transformableinto a continuous stream of product, even when that would beadvantageous for certain investigation methods.

[0067] The invention also provides an apparatus for the mixing processdescribed above.

[0068] The apparatus of the invention has:

[0069] i) storage vessels for each individual component of the mixtureto be prepared,

[0070] ii) mixing device for mixing all of the components of the mixtureto be prepared;

[0071] iii) lines for the individual components, leading from eachindividual storage vessel to the mixing device;

[0072] iv) in every line for every individual component, conveyingdevices whose conveying rate can be set individually; and

[0073] v) control device for the conveying devices, which controls theconveying rate of each conveying device independently of the others, andwhich sets the conveying rate of at least one conveying device variablyand periodically between a predetermined lower limiting value and apredetermined upper limiting value.

[0074] The achievement of the abovementioned objects is described by wayof example for a system with n components, using the diagram shown inFIG. 1.

[0075] Any desired mixing assembly may be used to prepare the mixture ofthe components.

[0076] In one particularly preferred embodiment, this is a continuousmixer.

[0077] Static mixers are suitable.

[0078] In one preferred embodiment of the process of the invention, themixing assembly is composed of at least one screw machine.

[0079] In one preferred embodiment, the screw machines used areextruders, particularly preferably twin-screw extruders.

[0080] The conveying devices serve to feed the mixing assembly withcomponents of the mixture to be formed, for example in the form ofpowder or liquid or pellets, either in pure form, or premixed inmasterbatches.

[0081] The feed of the component(s), for example of polymers and, whereappropriate, of other additives, takes place continuously.

[0082] The metering methods of the prior art may be used for the processof the invention, for feeding the individual components to the mixingassembly. A comprehensive description of metering systems used inindustry was published in 1989 in “Dosieren von Feststoffen(Schüttgütern) [Metering of (bulk) solids]” from the company Gericke.Supplementary to that publication, the VDI report “Kunststoffe imAutomobilbau” [Plastics in automotive construction], Vol. No.:4224(2000) includes an up-to-date section concerning the meteringsystems usually used. These publications are incorporated by way ofreference.

[0083] Within the metering process, a distinction is made between thesingle-stream metering process and the multistream metering process.

[0084] In the single-stream metering process, the polymers are meteredinto the main inlet of the mixing assembly together with the additives.For this, use is made of feed hoppers and/or ancillary input equipmentwith horizontal or vertical screws.

[0085] The multistream metering process is also termed fractionatedmetering or the split feed technique. Here, various constituents areadded separately.

[0086] A distinction is also made between volumetric metering andgravimetric metering.

[0087] In the case of volumetric metering, appropriately designed screwsfor pellets, powder, fiber, and chips have what are known asdecompactors, as required by the flow behavior of the bulk material.Besides screws, vibrating troughs or belt metering systems are also usedfor the volumetric metering of pellets, coarse-grained powder, fibers,or flakes.

[0088] Gravimetric metering equipment used comprises velocity-regulatedand weight-regulated metering belt weighers, metering screw weighers,differential metering weighers with screw or vibrating trough, andquasi-continuous hopper weighers.

[0089] The annular groove metering system is used for volumetric orgravimetric metering of very small amounts of powder (about 10 g/h),this being where screw metering systems fail. Liquid constituents arefed to the mixing assembly through, for example, volumetric meteringpumps.

[0090] If the metering pumps are regulated by means of a differentialweigher, gravimetric metering is also possible for the addition ofliquids.

[0091] Another possibility is pulsed or ramped addition of additives byway of other metering units.

[0092] By way of example, an ejector weigher is used for pulsedaddition.

[0093] In the metering process, a distinction is made betweengravimetric and volumetric addition.

[0094] The control device used for the conveying devices for theindependent regulation of the conveying rate of each conveying device,and for setting the periodically varying conveying rate of at least oneconveying device between a predetermined lower limiting value and apredetermined upper limiting value may be a data-processing system whichis conventional per se, for example an appropriately programmedcomputer.

[0095] The invention also provides the use of the process of theinvention for preparing substance libraries for high-throughputscreening and other combinatorial methods.

[0096] For this, it is preferable to produce moldings from mixtures bythe process of the invention, preferably in the form of film strips,extrudates, or pellets produced from these extrudates.

[0097] The mixture is preferably present in the form, for example, of anextrudate or of an unsupported film strip, so that these can easily beconverted, for example by chopping or stamping of the film strip, orpelletization of the extrudate, into discrete fractions if this isadvantageous for the subsequent processing or investigation.

[0098] The mixture prepared may be exposed for a certain period or overa certain distance downstream of the mixing assembly to a definedenvironment or treatment or treatment pathway.

[0099] In this process, the mixture may be exposed to certaintemperature and humidity conditions, to a temperature profile, to one ormore liquids, to moisture, to one or more gases, to one or more solids,or to mixtures of liquids and gases and solids, or to one or more typesof electromagnetic radiation.

[0100] In this context, liquids or solids may be any of the organic orinorganic liquid and/or solid substances and/or biological living matteror substances. Another possible treatment is a mechanical load.

[0101] The mixtures prepared according to the invention areadvantageously polymer formulations.

[0102] Polymer formulations are mixtures of a polymer with one or moreother polymers and/or with organic and/or inorganic additives.

[0103] The additives may be liquid or solid, and their processingproperties may vary widely.

[0104] Examples of processing properties are viscosity, density or, inthe case of liquids, surface tension, or, in the case of solidadditives, grain size, grain shape, grain size distribution, hardness,flowability, adhesion, or bulk density.

[0105] The additives give the polymer formulations the propertiesdemanded by the respective application.

[0106] Examples which may be mentioned of the large number of additivesknown in the prior art are fillers, which may be used in the form ofbeads, fibers, or lamellae, with dimensions of from 10 nm to a fewmillimeters. They are used mainly to adjust the mechanical properties ofthe polymer formulations.

[0107] Examples of other additives are light stabilizers, in particularstabilizers to prevent damage by UV and visible light, flame retardants,processing aids, pigments, lubricants and friction additives, couplingagents, impact modifiers, flow agents, mold-release agents, nucleatingagents, acid scavengers, base scavengers, antioxidants.

[0108] These additives for plastics are described by way of example byH. Zweifel in: Plastics Additives Handbook, 5th edition, Hanser Verlag2000, incorporated herein by way of reference.

[0109] Other additives which may be used are thermoplastic and/ornon-thermoplastic polymers, in particular thermoplastic polymers, thuspreparing blends and polymer alloys with concentration gradients.

[0110] For the purposes of the invention, the term polymersfundamentally includes all of the known, synthetic, naturally occurring,and modified naturally occurring polymers, i.e. thermoplastic orthermoset polymers, including elastomeric polymers.

[0111] Examples of thermoset polymers are epoxy resins, phenolic resins,or alkyd resins.

[0112] It is particularly preferable to use thermoplastic polymers whichcan be processed by melt extrusion.

[0113] By way of example, mention may be made of:

[0114] polylactones, such as poly(pivalolactone), poly(caprolactone);

[0115] polyurethanes, such as the polymerization products of thediisocyanates, e.g. of naphthalene 1,5-diisocyanate; p-phenylenediisocyanates; m-phenylene diisocyanate, tolylene 2,4-diisocyanate,tolylene 2,6-diisocyanate, diphenylmethane 4,4′-diisocyanate,3,3′-dimethylbiphenyl 4,4′-diisocyanate, diphenylisopropylidene4,4′-diisocyanate, 3,3′-dimethyldiphenyl 4,4′-diisocyanate,3,3′-dimethyldiphenylmethane 4,4′-diisocyanate, 3,3′-dimethoxybiphenyl4,4′-diisocyanate, dianisidine diisocyanate, toluidine diisocyanate,hexamethylene diisocyanate, 4,4′-diisocyanatodiphenylmethane,hexamethylene 1,6-diisocyanate, or dicyclohexylmethane4,4′-diisocyanate, with long-chain diols, for example withpoly(tetramethylene adipate), poly(ethylene adipate), poly(butylene1,4-adipate), poly(ethylene succinate), poly(butylene 2,3-succinate),with polyether diols, and/or with one or more diols such as ethyleneglycol, propylene glycol, and/or with a polydiol, such as diethyleneglycol, triethylene glycol, and/or tetraethylene glycol;

[0116] polycarbonates, such as poly[methanebis(phenyl 4-carbonate)],poly[1,1-etherbis(phenyl 4-carbonate)], poly[diphenylmethanebis(phenyl4-carbonate)], poly[1,1-cyclohexanebis(phenyl carbonate)];

[0117] polysulfones, such as the reaction product of the sodium salt of2,2-bis(4-hydroxyphenyl)propane or of 4,4′-dihydroxydiphenyl ether with4,4′-dichlorodiphenyl sulfone;

[0118] polyethers, polyketones, and polyether ketones, such aspolymerization products of hydroquinone, of 4,4′-dihydroxybiphenyl, of4,4′-dihydroxybenzophenone, or of 4,4′-dihydroxydiphenylsulfone withdihalogenated, in particular difluorinated or dichlorinated, aromaticcompounds of the type represented by 4,4′-dihalodiphenyl sulfone,4,4′-dihalodibenzophenone, bis(4,4′-dihalobenzoyl)benzene,4,4′-dihalobiphenyl;

[0119] polyamides, such as poly(4-aminobutanoic acid),poly(hexamethyleneadipamide), poly(6-aminohexanoic acid),poly(m-xylyleneadipamide), poly(p-xylylenesebacamide),poly(2,2,2-trimethylhexamethyleneterephthalamide),poly(meta-phenyleneisophthalamide) (NOMEX),poly(p-phenyleneterephthalamide) (KEVLAR);

[0120] polyesters, such as poly(ethylene acetate), poly(ethylene1,5-naphthalate), poly(cyclohexane-1,4-dimethylene terephthalate),poly(ethylene oxybenzoate) (A-TELL), poly(parahydroxybenzoate) (EKONOL),poly(cyclohexylidene-1,4-dimethylene terephthalate) (KODEL),polyethylene terephthalate, polybutylene terephthalate;

[0121] poly(arylene oxides), such as poly(2,6-dimethylphenylene1,4-oxide), poly(2,6-diphenylphenylene 1,4-oxide);

[0122] homo- and copolyacetals, such as oxymethylene polymers;

[0123] liquid-crystalline polymers, such as the polycondensationproducts from the group of monomers consisting of terephthalic acid,isophthalic acid, naphthalene-1,4-carboxylic acid,naphthalene-2,6-dicarboxylic acid, biphenyl-4,4′-dicarboxylic acid,4-hydroxybenzoic acid, 6-hydroxy-2-naphthalenedicarboxylic acid,hydroquinone, 4,4′-dihydroxybiphenyl, 4-aminophenol;

[0124] poly(arylene sulfides), such as poly(phenylene sulfide),poly(phenylene sulfide ketone), poly(phenylene sulfide sulfone);

[0125] polyetherimides;

[0126] vinyl polymers and their copolymers, such as polyvinyl acetate,polyvinyl chloride, polyvinyl butyral, polyvinylidene chloride,ethylene-vinyl acetate copolymers;

[0127] polyacrylic derivatives, such as polyacrylate and its copolymers,e.g. polyethyl acrylate, poly(n-butyl acrylate), polymethylmethacrylate, polyethyl methacrylate, poly(n-butyl methacrylate),poly(n-propyl methacrylate), polyacrylonitrile, water-insolubleethylene-acrylic acid copolymers, water-insoluble ethylene-vinyl alcoholcopolymers, acrylonitrile copolymers, methyl methacrylate-styrenecopolymers, ethylene-ethyl acrylate copolymers,acrylonitrile-butadiene-styrene copolymers;

[0128] polyolefins, such as polyethylene, in particular high-density andlow-density poly(ethylene), polypropylene, chlorinated low-densitypoly(ethylene), poly(4-methyl-1-pentene), poly(styrene);

[0129] water-insoluble ionomers;

[0130] poly(epichlorohydrin);

[0131] furan polymers, such as poly(furan);

[0132] cellulose esters, such as cellulose acetate, cellulose acetatebutyrate, cellulose propionate;

[0133] silicones, such as poly(dimethylsiloxane),poly(dimethylsiloxane-co-phenylmethylsiloxane);

[0134] protein thermoplastics;

[0135] and also all of the mixtures and alloys (miscible and immiscibleblends) of two or more of the polymers mentioned.

[0136] For the purposes of the invention, polymers also encompasselastomers derived, for example, from one or more of the followingpolymers:

[0137] brominated butyl rubber, chlorinated butyl rubber, polyurethaneelastomers, fluoroelastomers, polyester elastomers, elastomericpolyvinyl chloride, butadiene-acrylonitrile elastomers, siliconeelastomers, poly(butadiene), poly(isobutylene), ethylene-propylenecopolymers, ethylene-propylene-diene terpolymers, sulfonatedethylene-propylene-diene terpolymers, poly(chloroprene),poly(2,3-dimethylbutadiene), poly(butadiene-pentadiene),chlorosulfonated poly(ethylenes), poly(sulfide) elastomers, blockcopolymers, built up from segments of amorphous or of (semi)crystallineblocks, such as poly(styrene), poly(vinyltoluene),poly(tert-butylstyrene), polyesters, and the like, and of elastomericblocks, such as poly(butadiene), poly(isoprene), ethylene-propylenecopolymers, ethylene-butylene copolymers, ethylene-isoprene copolymers,and hydrogenated derivatives of these, e.g. SEBS, SEPS, SEEPS, and alsohydrogenated ethylene-isoprene copolymers with a relatively highproportion of 1,2-linked isoprene, polyethers, such as the productsmarketed by Kraton Polymers with the trade name KRATON®.

1. A process for the continuous preparation of mixtures from at leasttwo components, encompassing the steps of: a) charging the individualcomponents to storage vessels, b) introducing each individual componentby way of a conveying device for that component into a mixing device, c)varying the conveying rate of at least one conveying device in such away that this conveying rate varies periodically between a lower and anupper limiting value, and d) mixing the individual components in themixing device.
 2. The process as claimed in claim 1, wherein thevariation of the conveying rate of one conveying device continuouslyrises or falls, and wherein the variation in the conveying rate of allof the other conveying devices is periodic.
 3. The process as claimed inclaim 1, wherein the variation of the conveying rate of variousconveying devices is periodic and wherein the frequencies of thevariations differ from one another.
 4. The process as claimed in claim1, wherein the variation of the conveying rate of at least one conveyingdevice, preferably of all of the periodic variations, corresponds to asawtooth function or a sine function, the periods thereof preferablybeing constant over time.
 5. The process as claimed in claim 1, whereinthe variation of the conveying rate of at least one conveying devicecorresponds to a periodic step function whose periods and step intervalsare preferably constant over time.
 6. The process as claimed in claim 1,wherein the periods or step intervals for the variation of the conveyingrates of the individual conveying devices are an integral multiple of abase period, where the ratio of any two desired periods or stepintervals for the variation of the conveying rate of the conveyingdevices, or the ratio of a period and a step interval for the variationof the conveying rate of two conveying devices, is preferably equal tohalf of a whole number, and is in particular 0.5, or 1.5, or 2.5.
 7. Theprocess as claimed in claim 1, wherein the frequency ratio of twoperiodic variations of the conveying rate of two conveying devices isproportional to the compositional resolution desired.
 8. The process asclaimed in claim 1, wherein the total conveying rate of all of theconveying devices is constant over time.
 9. The process as claimed inclaim 1, wherein at least one component is a liquid, a conveyable solid,and/or a gas.
 10. The process as claimed in claim 9, wherein at leastone component is a polymer melt, and wherein at least one othercomponent is an additive.
 11. An apparatus for carrying out the processas claimed in claim 1, encompassing the following units: i) storagevessels for each individual component of the mixture to be prepared, ii)mixing device for mixing all of the components of the mixture to beprepared; iii) lines for the individual components, leading from eachindividual storage vessel to the mixing device; iv) in every line forevery individual component, conveying devices whose conveying rate canbe set individually; and v) control device for the conveying devices,which controls the conveying rate of each conveying device independentlyof the others, and which sets the conveying rate of at least oneconveying device variably and periodically between a predetermined lowerlimiting value and a predetermined upper limiting value.
 12. Theapparatus as claimed in claim 11, wherein the mixing device is a staticmixer.
 13. The apparatus as claimed in claim 11, wherein the mixingdevice is a screw extruder.
 14. The use of the process as claimed inclaim 1 for producing substance libraries for high-throughput screeningand other combinatorial methods.
 15. The use as claimed in claim 14,wherein moldings are produced, preferably in the form of film strips,extrudates, or pellets produced from these extrudates.
 16. The use asclaimed in claim 15, wherein the molding is an extrudate or anunsupported film strip, from which discrete fractions are produced bychopping or stamping, or by pelletizing.